tbuckley/cabot-search huggingface dataset:
Biomechanically‐Adapted Immunohydrogels Reconstructing Myelin Sheath for Peripheral Nerve Regeneration
Authors: Yifan Wang, Zhiwen Yan, Wenjun Liu, Chunlin Liu, Nan Xu, Yixian Wu, Fengbo Sun, Xiumei Wang, Yun Qian, Le Jiang, Xiaodan Sun
Journal: Advanced Healthcare Materials (2022)

Myelin sheath reconstruction plays an important role in peripheral nerve regeneration. But the hindered reconstruction of myelin sheath, due to the inadequate repair phenotypes of macrophages and Schwann cells after peripheral nerve injury, often causes poor functional nerve recovery. Here, biomechanically-adapted immunohydrogels are prepared as the FK506-loaded platforms and nerve tissue engineering scaffolds to reconstruct myelin sheath for peripheral nerve regeneration. By immunofluorescent staining, an increase in the proportion of F4/80+ markers reveals that the biomechanically-adapted scaffolds facilitate recruitment of macrophages. Furthermore, the high Interleukin 10 (IL-10) mRNA expression level suggests the anti-inflammation learning effects of FK506 in vitro, which is further confirmed by a high CD206/TNF-α ratio in the FK506 Gel group in vivo. The immune learning effects are positively related to the increase in compactness and thickness of myelin sheath, indicating the synergy of structural reconstruction of myelin sheath and M2 phenotype polarization of macrophages. All these data indicate that the biomechanically-adapted immunohydrogels enhance recruitment of macrophages, educate M2 polarization of macrophages and promote a neuroprotective environment, which in consequence reconstructs myelin sheath for peripheral nerve regeneration.
Assessing Human Genome-wide Variation in the Massim Region of Papua New Guinea and Implications for the Kula Trading Tradition
Authors: Dang Liu, Benjamin M Peter, Wulf Schiefenhövel, Manfred Kayser, Mark Stoneking
Journal: Molecular Biology and Evolution (2022)

Abstract The Massim, a cultural region that includes the southeastern tip of mainland Papua New Guinea (PNG) and nearby PNG offshore islands, is renowned for a trading network called Kula, in which different valuable items circulate in different directions among some of the islands. Although the Massim has been a focus of anthropological investigation since the pioneering work of Malinowski in 1922, the genetic background of its inhabitants remains relatively unexplored. To characterize the Massim genomically, we generated genome-wide SNP data from 192 individuals from 15 groups spanning the entire region. Analyzing these together with comparative data, we found that all Massim individuals have variable Papuan-related (indigenous) and Austronesian-related (arriving ∼3,000 years ago) ancestries. Individuals from Rossel Island in southern Massim, speaking an isolate Papuan language, have the highest amount of a distinct Papuan ancestry. We also investigated the recent contact via sharing of identical by descent (IBD) genomic segments and found that Austronesian-related IBD tracts are widely distributed geographically, but Papuan-related tracts are shared exclusively between the PNG mainland and Massim, and between the Bismarck and Solomon Archipelagoes. Moreover, the Kula-practicing groups of the Massim show higher IBD sharing among themselves than do groups that do not participate in Kula. This higher sharing predates the formation of Kula, suggesting that extensive contact between these groups since the Austronesian settlement may have facilitated the formation of Kula. Our study provides the first comprehensive genome-wide assessment of Massim inhabitants and new insights into the fascinating Kula system.
Diagnostic accuracy of telemedicine for detection of surgical site infection: a systematic review and meta-analysis
Authors: Ross Lathan, Misha Sidapra, Marina Yiasemidou, Judith Long, Joshua Totty, George Smith, Ian Chetter
Journal: npj Digital Medicine (2022)

The Sars-CoV-2 pandemic catalysed integration of telemedicine worldwide. This systematic review assesses it's accuracy for diagnosis of Surgical Site Infection (SSI). Databases were searched for telemedicine and wound infection studies. All types of studies were included, only paired designs were taken to meta-analysis. QUADAS-2 assessed methodological quality. 1400 titles and abstracts were screened, 61 full text reports were assessed for eligibility and 17 studies were included in meta-analysis, mean age was 47.1 ± 13.3 years. Summary sensitivity and specificity was 87.8% (95% CI, 68.4-96.1) and 96.8% (95% CI 93.5-98.4) respectively. The overall SSI rate was 5.6%. Photograph methods had lower sensitivity and specificity at 63.9% (95% CI 30.4-87.8) and 92.6% (95% CI, 89.9-94.5). Telemedicine is highly specific for SSI diagnosis is highly specific, giving rise to great potential for utilisation excluding SSI. Further work is needed to investigate feasibility telemedicine in the elderly population group.
Genomic landscape of patients with FLT3-mutated acute myeloid leukemia (AML) treated within the CALGB 10603/RATIFY trial
Authors: Nikolaus Jahn, Ekaterina Jahn, Maral Saadati, Lars Bullinger, Richard A. Larson, Tiziana Ottone, Sergio Amadori, Thomas W. Prior, Joseph M. Brandwein, Frederick R. Appelbaum, Bruno C. Medeiros, Martin S. Tallman, Gerhard Ehninger, Michael Heuser, Arnold Ganser, Celine Pallaud, Insa Gathmann, Julia Krzykalla, Axel Benner, Clara D. Bloomfield, Christian Thiede, Richard M. Stone, Hartmut Döhner, Konstanze Döhner
Journal: Leukemia (2022)

Abstract The aim of this study was to characterize the mutational landscape of patients with FLT3 -mutated acute myeloid leukemia (AML) treated within the randomized CALGB 10603/RATIFY trial evaluating intensive chemotherapy plus the multi-kinase inhibitor midostaurin versus placebo. We performed sequencing of 262 genes in 475 patients: mutations occurring concurrently with the FLT3 -mutation were most frequent in NPM1 (61%), DNMT3A (39%), WT1 (21%), TET2 (12%), NRAS (11%), RUNX1 (11%), PTPN11 (10%), and ASXL1 (8%) genes. To assess effects of clinical and genetic features and their possible interactions, we fitted random survival forests and interpreted the resulting variable importance. Highest prognostic impact was found for WT1 and NPM1 mutations, followed by white blood cell count, FLT3 mutation type (internal tandem duplications vs. tyrosine kinase domain mutations), treatment (midostaurin vs. placebo), ASXL1 mutation, and ECOG performance status. When evaluating two-fold variable combinations the most striking effects were found for WT1 : NPM1 (with NPM1 mutation abrogating the negative effect of WT1 mutation), and for WT1 :treatment (with midostaurin exerting a beneficial effect in WT1 -mutated AML). This targeted gene sequencing study provides important, novel insights into the genomic background of FLT3 -mutated AML including the prognostic impact of co-mutations, specific gene–gene interactions, and possible treatment effects of midostaurin.
The Diagnostic Impact of Epigenomics in Pituicyte-derived Tumors: Report of an Unusual Sellar Lesion with Extensive Hemorrhage and Necrotic Debris
Authors: Matthias Dottermusch, Roman Rotermund, Franz L. Ricklefs, Annika K. Wefers, Wolfgang Saeger, Jörg Flitsch, Markus Glatzel, Jakob Matschke
Journal: Endocrine Pathology (2022)
Letter to the Editor: Overlooking the important factor: Hypoxia
Authors: Yusheng Guo, Yanqiao Ren, Xiangjun Dong, Xuefeng Kan, Chuansheng Zheng
Journal: Hepatology (2022)

Guo, Yusheng; Ren, Yanqiao; Dong, Xiangjun; Kan, Xuefeng; Zheng, Chuansheng Author Information
Estrogen Receptor Alpha Gene Amplification Is an Independent Predictor of Long-Term Outcome in Postmenopausal Patients with Endocrine-Responsive Early Breast Cancer
Authors: Christian F. Singer, Frederik Holst, Stefan Steurer, Eike C. Burandt, Sigurd F. Lax, Raimund Jakesz, Margaretha Rudas, Herbert Stöger, Richard Greil, Guido Sauter, Martin Filipits, Ronald Simon, Michael Gnant
Journal: Clinical Cancer Research (2022)

Estrogen receptor (ER) expression is a prognostic parameter in breast cancer, and a prerequisite for the use of endocrine therapy. In ER+ early breast cancer, however, no receptor-associated biomarker exists that identifies patients with a particularly favorable outcome. We have investigated the value of ESR1 amplification in predicting the long-term clinical outcome in tamoxifen-treated postmenopausal women with endocrine-responsive breast cancer.394 patients who had been randomized into the tamoxifen-only arm of the prospective randomized ABCSG-06 trial of adjuvant endocrine therapy with available formalin-fixed, paraffin-embedded tumor tissue were included in this analysis. IHC ERα expression was evaluated both locally and in a central lab using the Allred score, while ESR1 gene amplification was evaluated by FISH analysis using the ESR1/CEP6 ratio indicating focal copy number alterations.Focal ESR1 copy-number elevations (amplifications) were detected in 187 of 394 (47%) tumor specimens, and were associated with a favorable outcome: After a median follow-up of 10 years, women with intratumoral focal ESR1 amplification had a significantly longer distant recurrence-free survival [adjusted HR, 0.48; 95% confidence interval (CI), 0.26-0.91; P = 0.02] and breast cancer-specific survival (adjusted HR 0.47; 95% CI, 0.27-0.80; P = 0.01) as compared with women without ESR1 amplification. IHC ERα protein expression, evaluated by Allred score, correlated significantly with focal ESR1 amplification (P < 0.0001; χ2 test), but was not prognostic by itself.Focal ESR1 amplification is an independent and powerful predictor for long-term distant recurrence-free and breast cancer-specific survival in postmenopausal women with endocrine-responsive early-stage breast cancer who received tamoxifen for 5 years.
Immunogenicity and reactogenicity of heterologous immunization against SARS CoV-2 using Sputnik V, ChAdOx1-S, BBIBP-CorV, Ad5-nCoV, and mRNA-1273
Authors: Carla A. Pascuale, Augusto Varese, Diego S. Ojeda, Marina E. Pasinovich, Laura Lopez, Andres H. Rossi, Pamela E. Rodriguez, Esteban A. Miglietta, Ignacio Mazzitelli, Facundo Di Diego Garcia, Lautaro Sanchez, Santiago Oviedo Rouco, María Mora Gonzalez Lopez Ledesma, Juan Pablo Zurano, Bianca Mazzitelli, Graciela Scruzzi, Paula Barbero, Diego Cardozo, Sandra Gallego, Mariel Borda, Miguel Diaz, Francisco Ridao, Angela Brigido Rosales, Jorge Bhon, Juan M. Talia, María E. Diangelo, María A. Lacaze, Balanzino Aime, Sebastian Isaac Gutierrez, Regina Ercole, Rosana Toro, Lorena Tau, Laura Delaplace, Malena Ferreyra Compagnucci, Celeste Sartori, Isabel Desimone, Cecilia Echegoyen, Pilar Velazquez, Clarisa Testa, Daniela Hozbor, Guillermo Docena, Carlos H. Laino, Nicolas Kreplak, Marina Pifano, Gabriela Barbas, Analía Rearte, Carla Vizzotti, Juan M. Castelli, Jorge Geffner, Andrea V. Gamarnik
Journal: Cell Reports Medicine (2022)

Heterologous vaccination against coronavirus disease 2019 (COVID-19) provides a rational strategy to rapidly increase vaccination coverage in many regions of the world. Although data regarding messenger RNA (mRNA) and ChAdOx1 vaccine combinations are available, there is limited information about the combination of these platforms with other vaccines widely used in developing countries, such as BBIBP-CorV and Sputnik V. Here, we assess the immunogenicity and reactogenicity of 15 vaccine combinations in 1,314 participants. We evaluate immunoglobulin G (IgG) anti-spike response and virus neutralizing titers and observe that a number of heterologous vaccine combinations are equivalent or superior to homologous schemes. For all cohorts in this study, the highest antibody response is induced by mRNA-1273 as the second dose. No serious adverse events are detected in any of the schedules analyzed. Our observations provide rational support for the use of different vaccine combinations to achieve wide vaccine coverage in the shortest possible time.
Phase 1 Study of Chemoradiotherapy Combined with Nivolumab ± Ipilimumab for the Curative Treatment of Muscle-invasive Bladder Cancer
Authors: Ben-Max de Ruiter, Jons W. van Hattum, Djoeri Lipman, Theo M. de Reijke, R. Jeroen A. van Moorselaar, Erik J. van Gennep, A.H. Maartje Piet, Mila Donker, Tom van der Hulle, Jens Voortman, Jorg R. Oddens, Maarten C.C.M. Hulshof, Adriaan D. Bins
Journal: European Urology (2022)

Muscle-invasive bladder cancer (MIBC) has a poor prognosis. Chemoradiotherapy (CRT) in selected patients has comparable results to radical cystectomy. Results of neoadjuvant immune checkpoint inhibitors (ICIs) before radical cystectomy are promising. We hypothesize that ICI concurrent to CRT (iCRT) is safe and may improve treatment outcomes. To determine the safety of iCRT for MIBC. This multicenter, phase 1b, open-label, dose-escalation study determined the safety of CRT with three ICI regimens in patients with nonmetastatic (T2-4aN0-1) MIBC. Twenty-six patients received mitomycin C/capecitabine and 20 × 2.75 Gy to the bladder. Tolerability was evaluated in a cohort of up to ten patients. If two or fewer out of the first six patients or three or fewer of ten patients experienced dose-limiting toxicity (DLT), accrual continued in the next cohort. Patients received nivolumab 480 mg (NIVO480), nivolumab 3 mg/kg and ipilimumab 1 mg/kg (NIVO3 + IPI1), or nivolumab 1 mg/kg and ipilimumab 3 mg/kg (IPI3 + NIVO1). The primary endpoint was safety. Secondary objectives were response rate, disease-free survival, metastatic-free survival (MFS), and overall survival (OS). In the NIVO480 cohort, no patients experienced DLT. The NIVO3 + IPI1 2 patients experienced DLT, thrombocytopenia (grade 4), and asystole (grade 5). IPI3 + NIVO1 was discontinued after three out of six patients experienced DLT. Clinically significant adverse events (AEs) of grade ≥3 occurred in zero, three, and five patients in the NIVO480, NIVO3 + IPI1, and IPI3 + NIVO1 groups, respectively. The most common AEs were immune related and gastrointestinal. MFS and OS were 90% at 2 yr for NIVO480 and 90% at 1 yr for NIVO3 + IPI1. Limitations include the absence of a centralized pathology and radiology review, and a lack of biomarker analysis. In this dose-finding study of iCRT, the regimens of nivolumab monotherapy and nivolumab 3 mg/kg with ipilimumab 1 mg/kg have acceptable toxicity. We tested the safety of a new bladder-sparing treatment modality for muscle-invasive bladder cancer patients, combining immune checkpoint inhibitors simultaneously with chemoradiotherapy. We report that two regimens, nivolumab monotherapy and nivolumab 3 mg/kg with ipilimumab 1 mg/kg, are safe and can be used in phase 3 trials.
Age at Diagnosis of Hypertension by Race and Ethnicity in the US From 2011 to 2020
Authors: Xiaoning Huang, Kristen Lee, Michael C. Wang, Nilay S. Shah, Sadiya S. Khan
Journal: JAMA Cardiology (2022)

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Duration of Symptoms and Association With Positive Home Rapid Antigen Test Results After Infection With SARS-CoV-2
Authors: Lisa A. Cosimi, Christina Kelly, Samantha Esposito, Scott Seitz, Jacquelyn Turcinovic, John H. Connor, Deborah Hung
Journal: JAMA Network Open (2022)

This cohort study assesses the duration of symptoms and association with positive rapid antigen test results after SARS-CoV-2 infection.
Error in Abstract and Visual Abstract
Journal: JAMA Network Open (2022)

Terence J. O’Brien, MD; Samuel F. Berkovic, MD; Jacqueline A. French, MD; John A. Messenheimer, MD; Terri B. Sebree, BS; Marcel O. Bonn-Miller, PhD; Donna L. Gutterman, PharmD; STAR 1/STAR 2 Study Group; Manori Wijayath; Peter Patrikios; David Reutens; Joseph Frasca ; Udaya Seneviratne; Wendyl D’Souza ; Peter Bergin; Tim Anderson; Ian Rosemergy; Armin Nikpour ; Patrick Kwan; Fredrik Asztely ; Ernest Somerville
Errors in a Figure
Authors: Marco Fiore
Journal: JAMA Surgery (2022)

Hong Yang, MD; Hui Liu, MD; Yuping Chen, MD; Chengchu Zhu, MD; Wentao Fang, MD; Zhentao Yu, MD; Weimin Mao, MD; Jiaqing Xiang, MD; Yongtao Han, MD; Zhijian Chen, MD; Haihua Yang, MD; Jiaming Wang, MD; Qingsong Pang, MD; Xiao Zheng, MD; Huanjun Yang, MD; Tao Li, MD; Xu Zhang, MD; Qun Li, MD; Geng Wang, MD; Baofu Chen, MD; Teng Mao, MD; Min Kong, MD; Xufeng Guo, MD; Ting Lin, MD; Mengzhong Liu, MD; Jianhua Fu, MD, PhD
COVID-19 Vaccination Intentions, Concerns, and Facilitators Among US Parents of Children Ages 6 Months Through 4 Years
Authors: Aaron M. Scherer, Courtney A. Gidengil, Amber M. Gedlinske, Andrew M. Parker, Natoshia M. Askelson, Kate R. Woodworth, Christine A. Petersen, Megan C. Lindley
Journal: JAMA Network Open (2022)

Children aged 6 months through 4 years have become eligible for COVID-19 vaccination, but little is known about parental intentions regarding, concerns about, or facilitators to COVID-19 vaccination for this age group.To evaluate parental intentions, concerns, and facilitators for COVID-19 vaccination for children aged 6 months through 4 years and to help inform the US Centers for Disease Control and Prevention Advisory Committee on Immunization Practices' deliberations and recommendations for COVID-19 vaccination for children aged 6 months through 4 years.This cross-sectional study fielded an online survey from February 2 to 10, 2022, among a nonprobability sample of US parents of children aged 6 months through 4 years who were recruited through Qualtrics using quota-based sampling for respondent gender, race and ethnicity, and child age group.COVID-19 vaccination intentions, time to COVID-19 vaccination, COVID-19 vaccination concerns and facilitators, and trusted COVID-19 vaccination locations for children aged 6 months through 4 years.The final weighted sample of 2031 participants (73.5% participation rate) had more respondents who identified as male (985; weighted percentage, 54.8%) or White (696; weighted percentage, 66.2%), were aged 25 to 49 years (1628; weighted percentage, 85.6%), had at least a bachelor's degree (711; weighted percentage, 40.0%), lived in a metropolitan area (1743; weighted percentage, 82.9%) or the South (961; weighted percentage, 43.4%), or received at least 1 dose of a COVID-19 vaccine (1205; weighted percentage, 59.8%). Half of respondents (645; weighted percentage, 45.6%) indicated that they "definitely" or "probably" will vaccinate their child aged 6 months through 4 years once they became eligible. However, only one-fifth (396; weighted percentage, 19.0%) indicated they would get a COVID-19 vaccine for their child in this age group within 3 months of them becoming eligible for vaccination. Vaccine safety and efficacy were parents' top concerns, and receiving more information about safety and efficacy were the top facilitators to COVID-19 vaccination for this age group. A doctor's office or clinic and local pharmacy were the most trusted COVID-19 vaccination locations for this age group.These results suggest that only a minority of parents of children in this age group are eager to vaccinate their children within the first few months of eligibility, with widespread concerns about COVID-19 vaccination for this age group. Thus, considerable efforts to increase parental COVID-19 vaccine confidence for children aged 6 months through 4 years may be needed to maximize COVID-19 vaccination for this age group in the United States.
Joint Genetic Inhibition of PCSK9 and CETP and the Association With Coronary Artery Disease
Authors: Arjen J. Cupido, Laurens F. Reeskamp, Aroon D. Hingorani, Chris Finan, Folkert W. Asselbergs, G. Kees Hovingh, Amand F. Schmidt
Journal: JAMA Cardiology (2022)

Cholesteryl ester transfer protein inhibition (CETP) has been shown to increase levels of high-density lipoprotein cholesterol (HDL-C) and reduce levels of low-density lipoprotein cholesterol (LDL-C). Current LDL-C target attainment is low, and novel phase 3 trials are underway to investigate whether CETP inhibitors result in reduction of cardiovascular disease risk in high-risk patients who may be treated with PCSK9-inhibiting agents.To explore the associations of combined reduction of CETP and PCSK9 concentrations with risk of coronary artery disease (CAD) and other clinical and safety outcomes.Two-sample 2 × 2 factorial Mendelian randomization study in a general population sample that includes data for UK Biobank participants of European ancestry.Separate genetic scores were constructed for CETP and PCSK9 plasma protein concentrations, which were combined to determine the associations of combined genetically reduced CETP and PCSK9 concentrations with disease.Blood lipid and lipoprotein concentrations, blood pressure, CAD, age-related macular degeneration, type 2 diabetes, any stroke and ischemic stroke, Alzheimer disease, vascular dementia, heart failure, atrial fibrillation, chronic kidney disease, asthma, and multiple sclerosis.Data for 425 354 UKB participants were included; the median (IQR) age was 59 years (51-64), and 229 399 (53.9%) were female. The associations of lower CETP and lower PCSK9 concentrations with CAD are similar when scaled per 10-mg/dL reduction in LDL-C concentrations (CETP: odds ratio [OR], 0.74; 95% CI, 0.67 to 0.81; PCSK9: OR, 0.75; 95% CI, 0.71 to 0.79). Combined exposure to lower CETP and PCSK9 concentrations was associated with an additive magnitude with lipids and all outcomes, and we did not observe any nonadditive interactions, most notably for LDL-C (CETP: effect size, -1.11 mg/dL; 95% CI, -1.40 to -0.82; PCSK9: effect size, -2.13 mg/dL; 95% CI, -2.43 to -1.84; combined: effect size, -3.47 mg/dL; 95% CI, -3.76 to -3.18; P = .34 for interaction) and CAD (CETP: OR, 0.96; 95% CI, 0.94 to 1.00; PCSK9: OR, 0.94; 95% CI, 0.91 to 0.97; combined: OR, 0.90; 95% CI, 0.87 to 0.93; P = .83 for interaction). In addition, when corrected for multiple testing, lower CETP concentrations were associated with increased age-related macular degeneration (OR, 1.11; 95% CI, 1.04 to 1.19).Our results suggest that joint inhibition of CETP and PCSK9 has additive effects on lipid traits and disease risk, including a lower risk of CAD. Further research may explore whether a combination of CETP- and PCSK9-related therapeutics can benefit high-risk patients who are unable to reach treatment targets with existing options.